tbuckley/cabot-search huggingface dataset:
Optimized therapeutic strategy for patients with refractory or relapsed acute myeloid leukemia: long‐term clinical outcomes and health‐related quality of life assessment
Authors: Chen‐hua Yan, Yu Wang, Yu‐qian Sun, Yi‐fei Cheng, Xiao‐dong Mo, Feng‐rong Wang, Yu‐hong Chen, Yuan‐yuan Zhang, Ting‐ting Han, Huan Chen, Lan‐ping Xu, Xiao‐hui Zhang, Kai‐yan Liu, Xiao‐jun Huang
Journal: Cancer Communications (2022)

Abstract Background Patients with refractory or relapsed acute myeloid leukemia (AML) have poor survival, necessitating the exploration of optimized therapeutic strategy. Here, we aimed to investigate clinical outcomes and health‐related quality of life (HR‐QoL) after total therapy, which included allogeneic hematopoietic stem cell transplantation (allo‐HSCT), and prophylactic donor lymphocyte infusion (DLI) in the early phase after transplantation, followed by multiple measurable residual disease (MRD) and graft‐versus‐host disease (GvHD)‐guided DLIs. Methods Consecutive patients who had refractory or relapsed AML and had received non‐T‐cell‐depleted allo‐HSCT at Peking University Institute of Hematology were included in the study. If the patients achieved complete remission at 30 days after transplantation and had no evidence of relapse, severe infection, organ failure, and active GvHD at the time of planned DLI, prophylactic DLI was administered at 30 days after transplantation for human leukocyte antigen (HLA)‐matched related HSCT or at 45‐60 days after transplantation for haploidentical or unrelated HSCT. Subsequently, multiple DLIs were administered based on MRD results and whether they developed GvHD after transplantation. Results A total of 105 patients were eligible. Eighty‐seven patients received prophylactic DLI (group B), while 18 did not receive prophylactic DLI (group A). Among 105 patients, the cumulative incidence of grade 2‐4 acute GvHD and chronic GvHD was 40.6% (95% confidence interval [CI] = 30.6%‐50.6%) and 73.3% (95% CI = 67.4%‐79.2%), respectively. The cumulative incidence of relapse (CIR), transplant‐related mortality (TRM), and leukemia‐free survival (LFS) at 5 years after transplantation were 31.5% (95% CI = 21.9%‐41.1%), 22.1% (95% CI = 11.3%‐32.9%), and 46.4% (95% CI = 36.8%‐56.0%), respectively. In group B, the CIR, TRM, and LFS at 5 years after transplantation were 27.6% (95% CI = 17.6%‐37.6%), 21.6% (95% CI = 11.2%‐32.0%), and 50.8% (95% CI = 40.0%‐61.6%), respectively. At the end of follow‐up, 48 patients survived, and more than 90% of survivors had satisfactory recoveries of HR‐QoL. Conclusions Our study indicated that total therapy is not only associated with decreased CIR, comparable TRM, and better long‐term LFS, but also with satisfactory HR‐QoL for refractory or relapsed AML, compared with those of standard of care therapy reported previously. Therefore, total therapy may be an optimized therapeutic strategy for refractory or relapsed AML.
Association of Spike-Specific T Cells With Relative Protection From Subsequent SARS-CoV-2 Omicron Infection in Young Children
Authors: Alexander C. Dowell, Georgina Ireland, Jianmin Zuo, Paul Moss, Shamez Ladhani
Journal: JAMA Pediatrics (2022)

This cohort study investigates the risk of SARS-CoV-2 reinfection among young children with and without spike-specific T-cell responses.
Development of Combination Strategies for Focal Adhesion Kinase Inhibition in Diffuse Gastric Cancer
Authors: Ke Peng, Feifei Zhang, Yichen Wang, Pranshu Sahgal, Tianxia Li, Jin Zhou, Xiaoyan Liang, Yanxi Zhang, Nilay Sethi, Tianshu Liu, Haisheng Zhang, Adam J. Bass
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Diffuse gastric cancer (DGC) is an aggressive and frequently lethal subtype of gastric cancer. Because DGC often lacks genomic aberrations that indicate clear candidate therapeutic targets, it has been challenging to develop targeted therapies for this gastric cancer subtype. Our previous study highlighted the contribution of focal adhesion kinase (FAK) in the tumorigenesis of DGC and the potential efficacy of small-molecule FAK inhibitors. However, drug resistance to monotherapy often hinders the efficacy of treatment. Experimental Design: We generated a genome-scale library of open reading frames (ORF) in the DGC model of Cdh1−/−RHOAY42C/+ organoids to identify candidate mechanisms of resistance to FAK inhibition. Compensatory activated pathways were also detected following treatment with FAK inhibitors. Candidates were investigated by cotargeting in vitro and in vivo experiments using DGC. Results: We found that cyclin-dependent kinase 6 (CDK6) promoted FAK inhibitor resistance in ORF screen. In addition, FAK inhibitor treatment in DGC models led to compensatory MAPK pathway activation. Small-molecule CDK4/6 inhibitors or MAPK inhibitors effectively enhanced FAK inhibitor efficacy in vitro and in vivo. Conclusions: Our data suggest that FAK inhibitors combined with MAPK inhibitors or CDK4/6 inhibitors warrant further testing in clinical trials for DGC.
Molecular Diagnostic Yield of Exome Sequencing and Chromosomal Microarray in Cerebral Palsy
Authors: Siddharth Srivastava, Sara A. Lewis, Julie S. Cohen, Bo Zhang, Bhooma R. Aravamuthan, Maya Chopra, Mustafa Sahin, Michael C. Kruer, Annapurna Poduri
Journal: JAMA Neurology (2022)

There are many known acquired risk factors for cerebral palsy (CP), but in some cases, CP is evident without risk factors (cryptogenic CP). Early CP cohort studies report a wide range of diagnostic yields for sequence variants assessed by exome sequencing (ES) and copy number variants (CNVs) assessed by chromosomal microarray (CMA).To synthesize the emerging CP genetics literature and address the question of what percentage of individuals with CP have a genetic disorder via ES and CMA.Searched articles were indexed by PubMed with relevant queries pertaining to CP and ES/CMA (query date, March 15, 2022).Inclusion criteria were as follows: primary research study, case series with 10 or more nonrelated individuals, CP diagnosis, and ES and/or CMA data used for genetic evaluation. Nonblinded review was performed.Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for assessing data quality and validity. Data were extracted by a single observer.A separate meta-analysis was performed for each modality (ES, CMA). The primary outcome was proportion/molecular diagnostic yield (number of patients with a discovered genetic disorder divided by the total number of patients in the cohort), evaluated via meta-analysis of single proportions using random-effects logistic regression. A subgroup meta-analysis was conducted, using risk factor classification as a subgroup. A forest plot was used to display diagnostic yields of individual studies.In the meta-analysis of ES yield in CP, the overall diagnostic yield of ES among the cohorts (15 study cohorts comprising 2419 individuals from 11 articles) was 23% (95% CI, 15%-34%). The diagnostic yield across cryptogenic CP cohorts was 35% (95% CI, 27%-45%), compared with 7% (95% CI, 4%-12%) across cohorts with known risk factors (noncryptogenic CP). In the meta-analysis of CMA yield in CP, the diagnostic yield of CMA among the cohorts (5 study cohorts comprising 294 individuals from 5 articles) was 5% (95% CI, 2%-12%).Results of this systematic review and meta-analysis suggest that for individuals with cryptogenic CP, ES followed by CMA to identify molecular disorders may be warranted.
Trends in Autism Spectrum Disorder Among Children and Adolescents in the US From 2016 to 2020
Authors: Chenxi Li, Wen-Qiang He
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Recent nanoengineered diagnostic and therapeutic advancements in management of Sepsis
Authors: Mukesh Soni, Mayank Handa, Kamalinder K. Singh, Rahul Shukla
Journal: Journal of Controlled Release (2022)

COVID-19 acquired symptoms have affected the worldwide population and increased the load of Intensive care unit (ICU) patient admissions. A large number of patients admitted to ICU end with a deadly fate of mortality. A high mortality rate of patients was reported with hospital-acquired septic shock that leads to multiple organ failures and ultimately ends with death. The patients who overcome this septic shock suffer from morbidity that also affects their caretakers. To overcome these situations, scientists are exploring progressive theragnostic techniques with advanced techniques based on biosensors, biomarkers, biozymes, vesicles, and others. These advanced techniques pave the novel way for early detection of sepsis-associated symptoms and timely treatment with appropriate antibiotics and immunomodulators and prevent the undue effect on other parts of the body. There are other techniques like externally modulated electric-based devices working on the principle of piezoelectric mechanism that not only sense the endotoxin levels but also target them with a loaded antibiotic to neutralize the onset of inflammatory response. Recently researchers have developed a lipopolysaccharide (LPS) neutralizing cartridge that not only senses the LPS but also appropriately neutralizes with dual mechanistic insights of antibiotic and anti-inflammatory effects. This review will highlight recent developments in the new nanotechnology-based approaches for the diagnosis and therapeutics of sepsis that is responsible for the high number of deaths of patients suffering from this critical disease.
In silico identification and synthesis of a multi-drug loaded MOF for treating tuberculosis
Authors: Abhinav P. Acharya, Kutay B. Sezginel, Hannah P. Gideon, Ashlee C. Greene, Harrison D. Lawson, Sahil Inamdar, Ying Tang, Amy J. Fraser, Kush V. Patel, Chong Liu, Nathaniel L. Rosi, Stephen Y. Chan, JoAnne L. Flynn, Christopher E. Wilmer, Steven R. Little
Journal: Journal of Controlled Release (2022)
Anti-LGI1–Associated Myopathy in the Setting of Neuromuscular Hyperexcitability Syndrome
Authors: Peter Anderyas, Amy Halliday, Katrina Reardon
Journal: JAMA Neurology (2022)

This case report describes a patient with anti–leucine-rich glioma-inactivated 1 (LGI1)–associated hyperexcitability syndrome associated with myopathy.
Reimagining Children’s Rights in the US
Authors: Elizabeth Barnert, Joseph Wright, Charlene Choi, Jonathan Todres, Neal Halfon, Miriam A Abaya, Lola A Adedokun, Abdullah Akl, David T Alexander, Mayra E Alvarez, Laudan Y Aron, Colette L Auerswald, Gabriella Barbosa, Gabrielle C Battle, Dana M Bunnett, Giselle Chow, Dimitri A Christakis, Nathaniel Z Counts, Tezzaree S El-Amin Champion, Mark G Engman, Toby J Ewing, Chloe R Gentile-Montgomery, Blanca Godoy, Jeffrey L Goldhagen, Brian Gran, Giovanni Hernandez, Puja Iyer, Myra Jones-Taylor, Jasmin M Kemp, Kayla A Kirsch, Gerison Lansdown, Wendy Lazarus, Bruce Lesley, Joan Lombardi, Guadalupe López Hernández, Brianna N Mejia-Garzaro, Keaun Michael Brown, Xavier Morales, Melissa K Moulton, Matthew B Peiffer, Andrea R Peńa, Nikki Pitre, William F Porayouw, Lauren A Poterek, Sandy Santana, Rimsha S Sayed, Marieka S Schotland, Bernard L Thomas III, Dashuri (Dash) L Togi, Barbara Woodhouse, Adrianna Zhang
Journal: JAMA Pediatrics (2022)

Importance The US faces a pivotal moment of opportunity and risk regarding issues affecting children (aged 0-17 years). Although the US remains the only United Nations member state to not have ratified the Convention on the Rights of the Child (CRC), a child rights framework is essential for child health professionals seeking to advance many issues affecting children in the US. The Reimagining Children’s Rights project (2020-2021) conducted an in-depth environmental scan of relevant literature and policy analysis using the Three Horizons design process to assess strategies that could advance the rights and well-being of children in the US. The project was overseen by a steering committee and informed by an advisory committee composed of youth leaders and experts in children’s rights, advocacy, health, law, and a range of child-specific issues (eg, youth justice, early childhood development), who provided expert input on strategic considerations for advancing children’s rights. Observations Seven findings about advancing children’s rights in the US are notable, all reflecting current gaps and opportunities for using a whole-child rights framework in the US, even without formal adoption of the CRC. Actionable strategies, tactics, and tools to leverage sustainable change in the multitude of issue areas can advance the current state of children’s rights. High-potential strategies for catalyzing advancement of children’s rights include youth activism, innovations in governance and accountability, legislative action, impact litigation, place-based initiatives, education and public awareness, alignment with other children’s movements, and research. The child rights framework is unifying and adaptive to future unforeseen challenges. Conclusions and Relevance Children’s rights provide a powerful, synergistic framework for child health professionals—in partnership with youth and other leaders—to increase equity and protect the rights and well-being of all children in the US.
SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance
Authors: Marta J. Llorca-Cardenosa, Lauren I. Aronson, Dragomir B. Krastev, Jadwiga Nieminuszczy, John Alexander, Feifei Song, Malgorzata Dylewska, Ronan Broderick, Rachel Brough, Astrid Zimmermann, Frank T. Zenke, Bora Gurel, Ruth Riisnaes, Ana Ferreira, Theodoros Roumeliotis, Jyoti Choudhary, Stephen J. Pettitt, Johann de Bono, Andres Cervantes, Syed Haider, Wojciech Niedzwiedz, Christopher J. Lord, Irene Y. Chong
Journal: Cancer Research (2022)

Abstract Gastric cancer represents the third leading cause of global cancer mortality and an area of unmet clinical need. Drugs that target the DNA damage response, including ATR inhibitors (ATRi), have been proposed as novel targeted agents in gastric cancer. Here, we sought to evaluate the efficacy of ATRi in preclinical models of gastric cancer and to understand how ATRi resistance might emerge as a means to identify predictors of ATRi response. A positive selection genome-wide CRISPR-Cas9 screen identified candidate regulators of ATRi resistance in gastric cancer. Loss-of-function mutations in either SMG8 or SMG9 caused ATRi resistance by an SMG1-mediated mechanism. Although ATRi still impaired ATR/CHK1 signaling in SMG8/9-defective cells, other characteristic responses to ATRi exposure were not seen, such as changes in ATM/CHK2, γH2AX, phospho-RPA, or 53BP1 status or changes in the proportions of cells in S- or G2–M-phases of the cell cycle. Transcription/replication conflicts (TRC) elicited by ATRi exposure are a likely cause of ATRi sensitivity, and SMG8/9-defective cells exhibited a reduced level of ATRi-induced TRCs, which could contribute to ATRi resistance. These observations suggest ATRi elicits antitumor efficacy in gastric cancer but that drug resistance could emerge via alterations in the SMG8/9/1 pathway. Significance: These findings reveal how cancer cells acquire resistance to ATRi and identify pathways that could be targeted to enhance the overall effectiveness of these inhibitors.
Sex Hormones in Breast Cancer Immunity
Authors: Ebony Hargrove-Wiley, Barbara Fingleton
Journal: Cancer Research (2022)

Abstract Sex hormones, such as estrogens and androgens, regulate genomic and cellular processes that contribute to sex-specific disparities in the pathophysiology of various cancers. Sex hormones can modulate the immune signals and activities of tumor cells and tumor-associated leukocytes to support or suppress cancer progression. Therefore, hormonal differences between males and females play a crucial role in cancer immunity and in the response to therapies that exploit the intrinsic immune system to eliminate malignant cells. In this review, we summarize the impact of sex hormones in the breast cancer microenvironment, with a focus on how the hormonal environment affects tumor immunity. We also discuss the potential benefits of endocrine therapy used in combination with immunotherapy to strengthen the antitumor immune response.
Right Bundle-Branch Block Pattern in Precordial Leads and Left Bundle-Branch Block Pattern With Left Axis Deviation in Frontal Plane Leads—What Does This Mean?
Authors: Matheus Kiszka Scheffer, Mariana Fuziy Nogueira De Marchi, Ana Carolina Muniz Costa
Journal: JAMA Internal Medicine (2022)

This case report describes a patient in their 70s who presented to the emergency department with a history of syncope that occurred 7 days before admission.
Trends in Autism Spectrum Disorder Among Children and Adolescents in the US From 2016 to 2020—Reply
Authors: Qian Li, Yanmei Li, Wenhan Yang
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Nonenzymatic function of DPP4 promotes diabetes-associated cognitive dysfunction through IGF-2R/PKA/SP1/ERp29/IP3R2 pathway-mediated impairment of Treg function and M1 microglia polarization
Authors: Ya Hui, Zhiqiang Xu, Jiaxiu Li, Liuyu Kuang, Yuanmei Zhong, Yunyun Tang, Junjie Wei, Huimin Zhou, Tianpeng Zheng
Journal: Metabolism (2022)
Experiences With Prenatal Care Delivery Reported by Black Patients With Low Income and by Health Care Workers in the US
Authors: Alex Friedman Peahl, Michelle H. Moniz, Michele Heisler, Aalap Doshi, Gwendolyn Daniels, Martina Caldwell, Vanessa K. Dalton, Ana De Roo, Mary Byrnes
Journal: JAMA Network Open (2022)

Importance Black pregnant people with low income face inequities in health care access and outcomes in the US, yet their voices have been largely absent from redesigning prenatal care. Objective To examine patients’ and health care workers’ experiences with prenatal care delivery in a largely low-income Black population to inform care innovations to improve care coordination, access, quality, and outcomes. Design, Setting, and Participants For this qualitative study, human-centered design–informed interviews were conducted at prenatal care clinics with 19 low-income Black patients who were currently pregnant or up to 1 year post partum and 19 health care workers (eg, physicians, nurses, and community health workers) in Detroit, Michigan, between October 14, 2019, and February 7, 2020. Questions focused on 2 human-centered design phases: observation (understanding problems from the end user’s perspective) and ideation (generating novel potential solutions). Questions targeted participants’ experiences with the 3 goals of prenatal care: medical care, anticipatory guidance, and social support. An eclectic analytic strategy, including inductive thematic analysis and matrix coding, was used to identify promising strategies for prenatal care redesign. Main Outcomes and Measures Preferences for prenatal care redesign. Results Nineteen Black patients (mean [SD] age, 28.4 [5.9] years; 19 [100%] female; and 17 [89.5%] with public insurance) and 17 of 19 health care workers (mean [SD] age, 47.9 [15.7] years; 15 female [88.2%]; and 13 [76.5%] Black) completed the surveys. A range of health care workers were included (eg, physicians, doulas, and social workers). Although all affirmed the 3 prenatal care goals, participants reported failures and potential solutions for each area of prenatal care delivery. Themes also emerged in 2 cross-cutting areas: practitioners and care infrastructure. Participants reported that, ideally, care structure would enable strong ongoing relationships between patients and practitioners. Practitioners would coordinate all prenatal services, not just medical care. Finally, care would be tailored to individual patients by using care navigators, flexible models, and colocation of services to reduce barriers. Conclusions and Relevance In this qualitative study of low-income, Black pregnant people in Detroit, Michigan, and the health care workers who care for them, prenatal care delivery failed to meet many patients’ needs. Participants reported that an ideal care delivery model would include comprehensive, integrated services across the health care system, expanding beyond medical care to also include patients’ social needs and preferences.